ESC Congress 2017 In Review -- Main Edition - 22

Late-Breaking Science

Empagliflozin Reduces Adverse
HF Outcomes in Diabetes
Patients, Regardless of HF Risk
Written by Nicola Parry

Empagliflozin is a selective sodium-glucose cotransporter 2 inhibitor that reduces hyperglycaemia in patients
with type 2 diabetes (T2D) by reducing renal glucose
reabsorption, and thereby increasing urinary glucose
excretion. In the EMPA-REG OUTCOME trial, when compared with placebo, empagliflozin (10 or 25 mg daily)
was shown to significantly reduce the incidence of death
from cardiovascular [CV] causes and hospitalisation for
heart failure (HHF) in patients with T2D and established
CV risk (HR, 0.86; 95% CI, 0.74 to 0.99; P = .04 for superiority) [Zinman B et al. N Engl J Med. 2015].
Javed Butler, MD, MPH, Stony Brook School of Medicine,
Stony Brook, New York, USA, reported the results of an
analysis of data from patients in the EMPA-REG OUTCOME
trial demonstrating that the risk reductions seen in the
main study occur across all spectrums of HF risk [Fitchett
D et al. Eur Heart J. 2017].
The primary objective of this analysis was to investigate the effects of empagliflozin in patients across the
spectrum of HF and HF risk. Patients who did not have
HF at baseline (89.9%; 6,314 of 7,028) were stratified as
to their 5-year risk for incident HF using the 9-variable
Health ABC HF Risk score [Butler J et al. Circ Heart Fail.
2008; Kalogeropoulos A et al. Circ Heart Fail. 2010]; 67.2%
were classified as being at low-to-average (5-year HF risk

< 10%), 24.2% as high risk (10-20%), and 5.1% as very high
risk (≥ 20%). Patients with HF at baseline or those with
an incident HF episode during follow-up were grouped
and defined as patients with 'HF burden.' The outcomes
of HHF or CV death (excluding fatal stroke), HHF, and CV
death (including fatal stroke) were assessed in relation to
HF-baseline risk using a time-to-first-event approach. Data
were pooled for the empagliflozin dose groups.
Regardless of their HF risk category, empagliflozin
reduced the risk of the primary endpoint in patients
without HF at baseline. The effect was consistent across
all 3 groups: low-to-average HF (HR, 0.71; 95% CI, 0.52
to 0.96), high risk (HR, 0.52; 95% CI, 0.36 to 0.75), and
very high risk (HR, 0.55; 95% CI, 0.30 to 1.00; P for
interaction .4; Figure 1), occurred early and persisted for
the duration of the trial.
In the placebo group, the incident HF hospitalisation
rate or CV death risk per 100 patient-years increased with
increasing HF risk profile: 1.68 (95% CI, 1.31 to 2.10) in the
low-to-average risk group; 4.03 (95% CI, 3.06 to 5.13) in
the high-risk group; and 7.0 (95% CI, 4.33 to 10.29) in the
very-high-risk group. The incident HF hospitalisation rate
or CV death risk in those with prevalent baseline HF was
8.55 (95% CI, 6.33 to 11.11) per 100 patient-years.
These findings demonstrate that in patients with T2D
and established CV disease, a sizeable proportion without HF at baseline are at high or very high risk for HF
outcomes. Empagliflozin reduced HF hospitalisation rate
and CV death risk regardless the presence of HF at baseline and across the spectrum of HF risk in those without
HF, Dr Butler concluded.

Figure 1. Effect of Empagliflozin on Heart Failure Hospitalisation and Cardiovascular Death According to Heart Failure Risk
Empagliflozin
n with event/ Rate per
N analyzed (%)
1000
pt-yrs
HHF or CV Death
*
5-year HF risk according to baseline Health ABC risk score
Low to average (< 10%)
101/2864 (3.5)
12.0
High (10-20%)
60/1012 (5.9)
20.7
Very high (20%)
22/204 (10.8)
38.0
CV Death
**
5-year HF risk according to baseline Health ABC risk score
Low to average(< 10%)
High (10-20%)
Very high (20%)

Placebo
n with event/ Rate per
1000
N analyzed (%)
pt-yrs

68/1382 (4.9)
56/515 (11.3)
21/115 (18.3)

70/2864 (2.4)
46/1012 (4.5)

8.2
15.4

51/1382 (3.7)
41/515 (8.0)

14/204 (6.9)

23.6

15/115 (13.0)

Hazard Ratio

Hazard Ratio

(95% CI)

(95% CI)

Treatment by
Subgroup
Interaction

P = .4280

16.8
40.3

0.71 (0.52, 0.96)
0.52 (0.36, 0.75)

70.0

0.55 (0.30, 1.00)

12.4
27.3
47.2

0.65 (0.45, 0.94)
0.57 (0.36, 0.88)
0.49 (0.24, 1.02)

P = .7660

P = .3622

HFF
5-year HF risk according to baseline Health ABC risk score
Low to average (< 10%)
41/2864 (1.4)
4.9
High (10-20%)
Very high (20%)

* excluding fatal stroke
** including fatal stroke

23/1012 (2.3)
11/204 (5.4)

7.9
19.0

26/1382 (2.0)

6.9

0.71 (0.44, 1.14)

27/515 (5.2)
10/115 (8.7)

18.8
33.3

0.42 (0.24, 0.73)
0.61 (0.26, 1.45)
0.125

0.25

0.5

Favours empagliflozin

1

2

4

Favours placebo

ABC, Health ABC Heart Failure Risk score; CI, confidence interval; CV, cardiovascular; HF, heart failure; HHF, hospitalisation for heart failure; pt-yrs, patient-years.
Reprinted from Fitchett D et al. Effects of empagliflozin on risk for cardiovascular death and heart failure hospitalisation across the spectrum of heart failure risk in the
EMPA-REG OUTCOME trial. Eur Heart J. 2017; doi:10.1093/eurheartj/ehx511. By permission of Oxford University Press on behalf of the European Society of Cardiology.

22

October 2017

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